Glutathione-S-transferase M1 regulation of diesel exhaust particle-induced pro-inflammatory mediator expression in normal human bronchial epithelial cells

ABSTRACT: BACKGROUND: Diesel exhaust particles (DEP) contribute substantially to ambient particulate matter (PM) air pollution in urban areas. Inhalation of PM has been associated with increased incidence of lung disease in susceptible populations. We have demonstrated that the glutathione Stransferase M1 (GSTM1) null genotype could aggravate DEP-induced airway inflammation in human subjects. Given the critical role airway epithelial cells play in the pathogenesis of airway inflammation, we established the GSTM1 deficiency condition in primary bronchial epithelial cells from human volunteers with GSTM1 sufficient genotype (GSTM1+) using GSTM1 shRNA to determine whether GSTM1 deficiency could exaggerate DEP-induced expression of interleukin-8 (IL-8) and IL-1beta proteins. Furthermore, the mechanisms underlying GSTM1 regulation of DEP-induced IL-8 and IL-1beta expression were also investigated. METHODS: IL-8 and IL-1beta protein levels were measured using enzyme-linked immunosorbent assay. GSTM1 deficiency in primary human bronchial epithelial cells was achieved using lentiviral GSTM1 shRNA particles and verified using real-time polymerase chain reaction and immunoblotting. Intracellular reactive oxygen species (ROS) production was evaluated using flow cytometry. Phosphorylation of protein kinases was detected using immunoblotting. RESULTS: Exposure of primary human bronchial epithelial cells (GSTM1+) to 25-100 mug/ml DEP for 24 h significantly increased IL-8 and IL-1beta protein expression. Knockdown of GSTM1 in these cells further elevated DEP-induced IL-8 and IL-1beta expression, implying that GSTM1 deficiency aggravated DEP-induced pro-inflammatory response. DEP stimulation induced the phosphorylation of extracellular signal-regulated kinase (ERK) and Akt, the downstream kinase of phosphoinositide 3-kinase (PI3K), in GSTM1+ bronchial epithelial cells. Pharmacological inhibition of ERK kinase and PI3K activity blocked DEP-induced IL-8 and IL-1beta expression. DEP-induced ERK and Akt phosphorylation could be increased by GSTM1 knockdown. In addition, pretreatment of HBEC with the antioxidant N-acetyl cysteine significantly inhibited DEP-induced ERK and Akt phosphorylation, and subsequent IL-8 and IL-beta expression. CONCLUSION: GSTM1 regulates DEP-induced IL-8 and IL-1beta expression in primary human bronchial epithelial cells by modulation of ROS, ERK and Akt signaling.     

Tapping into past design experiences: knowledge sharing and creation during novice–expert design consultations

Designing is a knowledge-intensive activity. For novice design engineers, an important means of acquiring knowledge is to consult experienced colleagues. We observed novice?Cexpert consultations as part of three engineering projects in a large aerospace company. Seven meetings were analysed in detail regarding the design activity, the content, and the form of interaction. Although the meetings were initiated for the purpose of information seeking, this process amounted to only 8% of the time compared to knowledge creation between novices and experts (47% of meeting time), and contextual information sharing (45% of meeting time). Both experts and novices were found to contribute equally and interactively to the discussion and analysis of solutions. The analysis showed how the processes alternated in the meetings. We identified tentative patterns on how these consultation processes change over the course of the design process phases. The micro-level analysis of the design activities and form of interaction provided a deeper understanding of how the consultation processes are discursively produced by the experts and novices. Finally, implications for design engineering practitioners are derived and suggestions for further research are provided.     

为高速A/D转换器设计电源供应器

许多现今的应用装置都需要高速取样模拟数字转换器（ADC）的分辨率达到12位或是更高位数,这是因为较高的分辨率能够让用户开发出更为精确的系统量测。不幸的是．较高的分辨率也代表了系统将会对噪声更加的敏感。只要系统的分辨率提高1个位（例如从12位升至13位）,系统的敏感度就会以2的倍数增加。因此,在使用ADC进行设计时,设计厂商对于经常被遗忘的一种噪声源一系统电源供应的考虑就变得相当重要。     

First-principles study of point defects and Si site preference in Al3Ti

The formation energies of various point defects in Al₃Ti(D0₂₂) have been calculated by using first-principles calculation. The effects of vacancies on Si site preference were examined to better understand Si substitution behavior in Al₃Ti. The results show that, under Al-rich condition, the formation energy of antisite Al_Ti is the lowest than those of other point defects, and Ti vacancy is more preferred than Al vacancy. But Si prefers to occupy Al vacancy compared with Ti vacancy which causes a finite solubility of Si in Al₃Ti system. The calculation is instructive for the further improvements of process of Si removal.     

An evaluation of the Brief Symptom Inventory–18 using item response theory: Which items are most strongly related to psychological distress?

The psychometric structure of the Brief Symptom Inventory–18 (BSI-18; Derogatis, 2001) was investigated using Mokken scaling and parametric item response theory. Data of 487 outpatients, 266 students, and 207 prisoners were analyzed. Results of the Mokken analysis indicated that the BSI-18 formed a strong Mokken scale for outpatients and prisoners, indicating strong unidimensionality. For students, only the depression and anxiety items formed a medium Mokken scale. Parametric item response theory analyses showed that the best discriminating items came from the depression and anxiety subscales. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

What is moral about guilt? Acting “prosocially” at the disadvantage of others.

For centuries economists and psychologists have argued that the morality of moral emotions lies in the fact that they stimulate prosocial behavior and benefit others in a person's social environment. Many studies have shown that guilt, arguably the most exemplary moral emotion, indeed motivates prosocial behavior in dyadic social dilemma situations. When multiple persons are involved, however, the moral and prosocial nature of this emotion can be questioned. The present article shows how guilt can have beneficial effects for the victim of one's actions but also disadvantageous effects for other people in the social environment. A series of experiments, with various emotion inductions and dependent measures, all reveal that guilt motivates prosocial behavior toward the victim at the expense of others around—but not at the expense of oneself. These findings illustrate that a thorough understanding of the functioning of emotions is necessary to understand their moral nature. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Solid‐State Conversion Reaction to Enhance Charge Transfer in Electrochromic Materials

Interface engineering has attracted great interest and is essential for the fabrication of thin‐film devices, such as smart windows. In this study, a solid‐state conversion reaction for the development of an interlayer enriched with lithium peroxide (Li₂O₂) is presented for an electrochromic device. We demonstrate that efficient lithium insertion and electron transport can be achieved by the inclusion of a Li₂O₂‐rich interlayer between an active electrochromic material and Li ion solid‐state electrolyte layer. The presence of a Li₂O₂‐rich interlayer enhances electrochromic efficiency, kinetics, optical contrast, and bleached‐state transparency in a nickel oxide‐based electrochromic thin film. This work opens up new opportunities to enhance the functionalities of thin‐film devices by solid‐state conversion reactions.     

Specific sleepiness symptoms are indicators of performance impairment during sleep deprivation

Drivers are not always aware that they are becoming impaired as a result of sleepiness. Using specific symptoms of sleepiness might assist with recognition of drowsiness related impairment and help drivers judge whether they are safe to drive a vehicle, however this has not been evaluated. In this study, 20 healthy volunteer professional drivers completed two randomized sessions in the laboratory – one under 24 h of acute sleep deprivation, and one with alcohol. The Psychomotor Vigilance Task (PVT) and a 30 min simulated driving task (AusEdTM) were performed every 3–4 h in the sleep deprivation session, and at a BAC of 0.00% and 0.05% in the alcohol session, while electroencephalography (EEG) and eye movements were recorded. After each test session, drivers completed the Karolinska Sleepiness Scale (KSS) and the Sleepiness Symptoms Questionnaire (SSQ), which includes eight specific sleepiness and driving performance symptoms. A second baseline session was completed on a separate day by the professional drivers and in an additional 20 non-professional drivers for test–retest reliability. There was moderate test–retest agreement on the SSQ (r = 0.59). Significant correlations were identified between individual sleepiness symptoms and the KSS score (r values 0.50–0.74, p < 0.01 for all symptoms). The frequency of all SSQ items increased during sleep deprivation (χ² values of 28.4–80.2, p < 0.01 for all symptoms) and symptoms were related to increased subjective sleepiness and performance deterioration. The symptoms “struggling to keep your eyes open”, “difficulty maintaining correct speed”, “reactions were slow” and “head dropping down” were most closely related to increased alpha and theta activity on EEG (r values 0.49–0.59, p < 0.001) and “nodding off to sleep” and “struggling to keep your eyes open” were related to slow eye movements (r values 0.67 and 0.64, p < 0.001). Symptoms related to visual disturbance and impaired driving performance were most accurate at detecting severely impaired driving performance (AUC on ROC curve of 0.86–0.91 for detecting change in lateral lane position greater than the change at a BAC of 0.05%). Individual sleepiness symptoms are related to impairment during acute sleep deprivation and might be able to assist drivers in recognizing their own sleepiness and ability to drive safely.